Evidence map›Paper›PMID 33744937›Full record

ArticleCardiovascular research2022

Isolation and characterization of human embryonic stem cell-derived heart field-specific cardiomyocytes unravels new insights into their transcriptional and electrophysiological profiles.

Arash Pezhouman, James L Engel, Ngoc B Nguyen, Rhys J P Skelton, William Blake Gilmore, Rong Qiao, Debashis Sahoo, Peng Zhao, David A Elliott, Reza Ardehali

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cardiovascular research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.4field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
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  10. The Role of POPDC Proteins in Cardiac Pacemaking and Conduction.Journal of cardiovascular development and disease · 2021
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 2 countries.

Arash PezhoumanDivision of Cardiology, Department of Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.ORCID 0000-0001-9106-7136
James L EngelDivision of Cardiology, Department of Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.ORCID 0000-0002-7512-8127
Ngoc B NguyenDivision of Cardiology, Department of Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Rhys J P SkeltonDivision of Cardiology, Department of Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
William Blake GilmoreDivision of Cardiology, Department of Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.ORCID 0000-0002-0653-4439
Rong QiaoDivision of Cardiology, Department of Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Debashis SahooDepartments of Pediatrics and Computer Science and Engineering, University of California San Diego, La Jolla, CA 92093, USA.
Peng ZhaoDivision of Cardiology, Department of Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
David A ElliottMurdoch Children's Research Institute, The Royal Children's Hospital, Parkville, VIC 3052, Australia.
Reza ArdehaliDivision of Cardiology, Department of Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.ORCID 0000-0003-1318-4016
University of California, Los Angeles · USRoyal Children's Hospital · AUUniversity of California San Diego · US

Funding

Macrophage Polarization in Response to Infections and InflammationR01AI155696 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GHOSH, PRADIPTA, SAHOO, DEBASHIS · 2020 to 2024
$4.9M
Generation of mature human embryonic stem cell-derived left ventricular cardiomyocytes for transplantation in a large animal modelR01HL148714 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARDEHALI, REZA · 2019 to 2022
$2.2M
Summer Student Research on the Application of Boolean AnalysisR01GM138385 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SAHOO, DEBASHIS · 2020 to 2023
$2.0M
Precision therapeutics of inflammatory bowel disease guided by Boolean logicUG3TR003355 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DAS, SOUMITA, GHOSH, PRADIPTA · 2020 to 2022
$937k
Application of Boolean Networks to discover stem and progenitor cellsR00CA151673 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SAHOO, DEBASHIS · 2014 to 2016
$717k
Protective Effects of Neonatal Plasma in Ischemic Heart DiseaseF31HL144057 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI NGUYEN, NGOC BAO · 2018 to 2020
$115k
NCATS NIH HHS UG3 TR003355NCI NIH HHS R00 CA151673NHLBI NIH HHS F31 HL144057NHLBI NIH HHS R01 HL148714NIAID NIH HHS R01 AI155696NIGMS NIH HHS R01 GM138385
6 · The paper itself

Abstract

aimsWe prospectively isolate and characterize first and second heart field- and nodal-like cardiomyocytes using a double reporter line from human embryonic stem cells. Our double reporter line utilizes two important transcription factors in cardiac development, TBX5 and NKX2-5. TBX5 expression marks first heart field progenitors and cardiomyocytes while NKX2-5 is expressed in nearly all myocytes of the developing heart (excluding nodal cells). We address the shortcomings of prior work in the generation of heart field-specific cardiomyocytes from induced pluripotent stem cells and provide a comprehensive early developmental transcriptomic as well as electrophysiological analyses of these three populations. METHODS AND

resultsTranscriptional, immunocytochemical, and functional studies support the cellular identities of isolated populations based on the expression pattern of NKX2-5 and TBX5. Importantly, bulk and single-cell RNA sequencing analyses provide evidence of unique molecular signatures of isolated first and second heart field cardiomyocytes, as well as nodal-like cells. Extensive electrophysiological analyses reveal dominant atrial action potential phenotypes in first and second heart fields in alignment with our findings in single-cell RNA sequencing. Lastly, we identify two novel surface markers, POPDC2 and CORIN, that enable purification of cardiomyocytes and first heart field cardiomyocytes, respectively.

conclusionsWe describe a high-yield approach for isolation and characterization of human embryonic stem cell-derived heart field-specific and nodal-like cardiomyocytes. Obtaining enriched populations of these different cardiomyocyte subtypes increases the resolution of gene expression profiling during early cardiogenesis, arrhythmia modelling, and drug screening. This paves the way for the development of effective stem cell therapy to treat diseases that affect specific regions of the heart- or chamber-specific congenital heart defects.

Indexed as

Human Embryonic Stem CellsInduced Pluripotent Stem CellsAction PotentialsCell DifferentiationHumansMyocytes, CardiacCardiac differentiationCorinElectrophysiologyHeart field-specific cardiomyocyteshESCs

Identifiers

PMID33744937
PMCPMC9020202
OpenAlexW3136578409

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.